scholarly journals Thermodynamic analysis of protein-ligand binding interactions in complex biological mixtures using the stability of proteins from rates of oxidation

2012 ◽  
Vol 8 (1) ◽  
pp. 148-161 ◽  
Author(s):  
Erin C Strickland ◽  
M Ariel Geer ◽  
Duc T Tran ◽  
Jagat Adhikari ◽  
Graham M West ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Thermodynamic Analysis ◽  
Binding Interactions ◽  
Biological Mixtures ◽  
The Stability

scholarly journals Dissecting Molecular Determinants of Mutational Escape Mechanisms in the SARS-CoV-2 Spike Protein Complexes with Nanobodies: Atomistic Simulations and Ensemble-Based Deep Mutational Scanning of Protein Stability and Binding Interactions

2021 ◽  
Author(s):  
Gennady Verkhivker ◽  
Steve Agajanian ◽  
Deniz Yasar Oztas ◽  
Grace Gupta
Keyword(s):  
Molecular Mechanisms ◽  
Protein Complexes ◽  
Conformational Dynamics ◽  
Spike Protein ◽  
Atomistic Simulations ◽  
Binding Interactions ◽  
Mutational Profiling ◽  
Neutralizing Capacity ◽  
The Stability ◽  
Protein Response

Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this work, we combined atomistic simulations and conformational dynamics analysis with the ensemble-based mutational profiling of binding interactions for a diverse panel of SARS-CoV-2 spike complexes with nanobodies. Using this computational toolkit, we identified dynamic signatures and binding affinity fingerprints for the SARS-CoV-2 spike protein complexes with nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E+U, a biparatopic nanobody VHH VE, and a combination of CC12.3 antibody and VHH V/W nanobodies. Through ensemble-based deep mutational profiling of stability and binding affinities, we identify critical hotspots and characterize molecular mechanisms of SARS-CoV-2 spike protein binding with single ultra-potent nanobodies, nanobody cocktails and biparatopic nanobodies. By quantifying dynamic and energetic determinants of the SARS-CoV-2 S binding with nanobodies, we also examine the effects of circulating variants and escaping mutations. We found that mutational escape mechanisms may be controlled through structurally and energetically adaptable binding hotspots located in the host receptor-accessible binding epitope that are dynamically coupled to the stability centers in the distant epitope targeted by VHH U/V/W nanobodies. The results of this study suggested a mechanism in which through cooperative dynamic changes, nanobody combinations and biparatopic nanobody can modulate the global protein response and induce the increased resilience to common escape mutants.

scholarly journals Protein-ligand binding interactions of imidazolium salts with SARS CoV-2

Heliyon ◽  
2020 ◽  
Vol 6 (11) ◽  
pp. e05544
Author(s):  
Dhurairaj Satheesh ◽  
Annamalai Rajendran ◽  
Kasi Chithra
Keyword(s):  
Ligand Binding ◽  
Imidazolium Salts ◽  
Binding Interactions

Thermodynamic analysis of the effect of water activity on the stability of macadamia nut

2007 ◽  
Vol 81 (3) ◽  
pp. 566-571 ◽  
Author(s):  
Irma L. Domı´nguez ◽  
Ebner Azuara ◽  
Eduardo J. Vernon-Carter ◽  
Cesar I. Beristain
Keyword(s):  
Water Activity ◽  
Thermodynamic Analysis ◽  
Effect Of Water ◽  
Macadamia Nut ◽  
The Stability

Characterization of the r-state insulin hexamer and its derivatives. The hexamer is stabilized by heterotropic ligand binding interactions

Biochemistry ◽  
1991 ◽  
Vol 30 (27) ◽  
pp. 6636-6645 ◽  
Author(s):  
Mark L. Brader ◽  
Niels C. Kaarsholm ◽  
Robert W. K. Lee ◽  
Michael F. Dunn
Keyword(s):  
Ligand Binding ◽  
Binding Interactions

scholarly journals Thermodynamic analysis of the stability of planar interfaces between coexisting phases and its application to supercooled water

2019 ◽  
Vol 150 (22) ◽  
pp. 224503 ◽  
Author(s):  
Rakesh S. Singh ◽  
Jeremy C. Palmer ◽  
Athanassios Z. Panagiotopoulos ◽  
Pablo G. Debenedetti
Keyword(s):  
Thermodynamic Analysis ◽  
Supercooled Water ◽  
Coexisting Phases ◽  
The Stability

scholarly journals The interplay of electrostatic fields and binding interactions determining catalytic-site reactivity in actinidin. A possible origin of differences in the behaviour of actinidin and papain

1989 ◽  
Vol 259 (2) ◽  
pp. 443-452 ◽  
Author(s):  
D Kowlessur ◽  
M O'Driscoll ◽  
C M Topham ◽  
W Templeton ◽  
E W Thomas ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Ligand Binding ◽  
Transition State ◽  
Rate Constant ◽  
Ph Dependence ◽  
Order Rate Constant ◽  
Catalytic Site ◽  
Binding Interactions ◽  
Electrostatic Fields ◽  
Transition State Geometry

1. The pH-dependence of the second-order rate constant (k) for the reaction of actinidin (EC 3.4.22.14) with 2-(N'-acetyl-L-phenylalanylamino)ethyl 2'-pyridyl disulphide was determined and the contributions to k of various hydronic states were evaluated. 2. The data were used to assess the consequences for transition-state geometry of providing P2/S2 hydrophobic contacts in addition to hydrogen-bonding opportunities in the S1-S2 intersubsite region. 3. The P2/S2 contacts (a) substantially improve enzyme-ligand binding, (b) greatly enhance the contribution to reactivity of the hydronic state bounded by pKa 3 (the pKa characteristic of the formation of catalytic-site-S-/-ImH+ state) and pKa 5 (a relatively minor contributor in reactions that lack the P2/S2 contacts), such that the major rate optimum occurs at pH 4 instead of at pH 2.8-2.9, and (c) reveal the kinetic influence of a pKa approx. 6.3 not hitherto observed in reactions of actinidin. 4. Possibilities for the interplay of electrostatic effects and binding interactions in both actinidin and papain (EC 3.4.22.2) are discussed.

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